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Adipocyte-derived extracellular vesicles increase insulin secretion through transport of insulinotropic protein cargo

Author

Listed:
  • Konxhe Kulaj

    (Helmholtz Zentrum München
    German Center for Diabetes Research (DZD)
    University of Augsburg)

  • Alexandra Harger

    (Helmholtz Zentrum München
    German Center for Diabetes Research (DZD))

  • Michaela Bauer

    (Helmholtz Zentrum München
    German Center for Diabetes Research (DZD)
    University of Augsburg)

  • Özüm S. Caliskan

    (Helmholtz Zentrum München
    German Center for Diabetes Research (DZD))

  • Tilak Kumar Gupta

    (Max Planck Institute of Biochemistry)

  • Dapi Menglin Chiang

    (Technical University of Munich)

  • Edward Milbank

    (Helmholtz Zentrum München
    University of Augsburg)

  • Josefine Reber

    (Helmholtz Zentrum München)

  • Angelos Karlas

    (Helmholtz Zentrum München
    Technical University of Munich
    Klinikum rechts der Isar, Technical University of Munich
    Partner Site Munich Heart Alliance)

  • Petra Kotzbeck

    (Helmholtz Zentrum München
    Medical University of Graz)

  • David N. Sailer

    (Helmholtz Zentrum München
    Technical University of Munich)

  • Francesco Volta

    (Helmholtz Zentrum München
    University of Parma)

  • Dominik Lutter

    (Helmholtz Zentrum München
    German Center for Diabetes Research (DZD))

  • Sneha Prakash

    (Helmholtz Zentrum München
    German Center for Diabetes Research (DZD))

  • Juliane Merl-Pham

    (Helmholtz Zentrum München)

  • Vasilis Ntziachristos

    (Helmholtz Zentrum München
    Technical University of Munich
    Partner Site Munich Heart Alliance)

  • Hans Hauner

    (Technical University of Munich
    Technical University of Munich)

  • Michael W. Pfaffl

    (Technical University of Munich)

  • Matthias H. Tschöp

    (Helmholtz Zentrum München
    German Center for Diabetes Research (DZD)
    Technical University of Munich)

  • Timo D. Müller

    (Helmholtz Zentrum München
    German Center for Diabetes Research (DZD))

  • Stefanie M. Hauck

    (Helmholtz Zentrum München)

  • Benjamin D. Engel

    (Helmholtz Zentrum München
    University of Basel)

  • Jantje M. Gerdes

    (Helmholtz Zentrum München)

  • Paul T. Pfluger

    (Helmholtz Zentrum München
    German Center for Diabetes Research (DZD)
    Helmholtz Zentrum München
    Technical University of Munich)

  • Natalie Krahmer

    (Helmholtz Zentrum München
    German Center for Diabetes Research (DZD))

  • Kerstin Stemmer

    (Helmholtz Zentrum München
    German Center for Diabetes Research (DZD)
    University of Augsburg)

Abstract

Adipocyte-derived extracellular vesicles (AdEVs) are membranous nanoparticles that convey communication from adipose tissue to other organs. Here, to delineate their role as messengers with glucoregulatory nature, we paired fluorescence AdEV-tracing and SILAC-labeling with (phospho)proteomics, and revealed that AdEVs transfer functional insulinotropic protein cargo into pancreatic β-cells. Upon transfer, AdEV proteins were subjects for phosphorylation, augmented insulinotropic GPCR/cAMP/PKA signaling by increasing total protein abundances and phosphosite dynamics, and ultimately enhanced 1st-phase glucose-stimulated insulin secretion (GSIS) in murine islets. Notably, insulinotropic effects were restricted to AdEVs isolated from obese and insulin resistant, but not lean mice, which was consistent with differential protein loads and AdEV luminal morphologies. Likewise, in vivo pre-treatment with AdEVs from obese but not lean mice amplified insulin secretion and glucose tolerance in mice. This data suggests that secreted AdEVs can inform pancreatic β-cells about insulin resistance in adipose tissue in order to amplify GSIS in times of increased insulin demand.

Suggested Citation

  • Konxhe Kulaj & Alexandra Harger & Michaela Bauer & Özüm S. Caliskan & Tilak Kumar Gupta & Dapi Menglin Chiang & Edward Milbank & Josefine Reber & Angelos Karlas & Petra Kotzbeck & David N. Sailer & Fr, 2023. "Adipocyte-derived extracellular vesicles increase insulin secretion through transport of insulinotropic protein cargo," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-36148-1
    DOI: 10.1038/s41467-023-36148-1
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    References listed on IDEAS

    as
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    2. Thomas Thomou & Marcelo A. Mori & Jonathan M. Dreyfuss & Masahiro Konishi & Masaji Sakaguchi & Christian Wolfrum & Tata Nageswara Rao & Jonathon N. Winnay & Ruben Garcia-Martin & Steven K. Grinspoon &, 2017. "Correction: Corrigendum: Adipose-derived circulating miRNAs regulate gene expression in other tissues," Nature, Nature, vol. 545(7653), pages 252-252, May.
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